Endothelial dysfunction that is caused by insulin resistance, dyslipidemia, and hyperglycemia in Ceacam1−/− mice causes a reduction in endothelial nitric oxide (NO) levels due to impaired endothelial activation of IRS1/Akt/eNOS (endothelial nitric oxide synthase pathway), in addition to an imbalanced endothelin-1 (ET-1) receptor A/B expression [139]. The gene discussed is NOS3; the disease is Insulin resistance.